Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks

• ClinicalTrials.gov Identifier: NCT00168103
• Recruitment Status: Completed
• First Posted: September 14, 2005
• Results First Posted: August 24, 2010
• Last Update Posted: March 31, 2015
• Sponsor: CSL Behring
• Information provided by: CSL Behring

Study Description

Brief Summary:

HAE is a rare disorder characterized by functional C1 esterase inhibitor deficiency. If not treated adequately, the acute attacks of HAE can be life-threatening and may even result in fatalities, especially in case of swelling of the larynx. This clinical Phase 2/Phase 3 study was designed to provide clinically relevant data on dosing, efficacy and safety in subjects with HAE.

Condition or disease	Intervention/treatment	Phase
Hereditary Angioedema	Biological: C1 Esterase Inhibitor; Biological: Placebo	Phase 2; Phase 3

Detailed Description:

For each subject, only a single abdominal or facial attack was treated and evaluated. After receiving treatment, subjects were observed for a minimum of 4 hours, after which they could be discharged from the study center if they reported onset of symptom relief. Starting from 4 hours after treatment, subjects who reported insufficient or no symptom relief could receive a second dose of double-blind treatment (called "rescue medication") as follows: C1-INH 20 U/kg bw for subjects initially receiving placebo, C1-INH 10 U/kg bw for subjects initially receiving C1-INH 10 U/kg bw, and placebo for subjects initially receiving C1-INH 20 U/kg bw.

The study was defined to be successful if the primary outcome measure and at least one of the secondary outcome measures were met in the comparison between the C1-INH 20 U/kg bw group and the Placebo group.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks
• Study Start Date: June 2005
• Actual Primary Completion Date: October 2007
• Actual Study Completion Date: December 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: C1-INH 10 U/kg bw; 10 Units (U)/kg body weight (bw) dose	Biological: C1 Esterase Inhibitor; Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min.; Other Names: Berinert; Berinert P; CE1145
Experimental: C1-INH 20 U/kg bw; 20 U/kg bw dose	Biological: C1 Esterase Inhibitor; Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min.; Other Names: Berinert; Berinert P; CE1145
Placebo Comparator: Placebo	Biological: Placebo; Single application of physiological saline solution equivalent to the volume calculated for subjects in the C1-INH 20 U/kg bw arm.; Other Name: Physiological saline solution

Outcome Measures

Primary Outcome Measures :

1. Time to Start of Relief of Symptoms From HAE Attack [ Time Frame: Up to 24 h after start of study treatment ]
   The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief.

Secondary Outcome Measures :

1. Number of Subjects With Worsened Intensity of Clinical HAE Symptoms [ Time Frame: Baseline and between 2 and 4 h after start of study treatment ]
   Includes any worsening of intensity of at least 1 of the HAE symptoms present at baseline. Routinely checked symptoms included pain, nausea, vomiting, cramps, and diarrhea.
2. Number of Vomiting Episodes [ Time Frame: Within 4 h after start of study treatment ]

Other Outcome Measures:

1. Time to Complete Resolution of All HAE Symptoms, Including Pain [ Time Frame: Up to 24 h after start of study treatment ]
   Complete resolution of symptoms was determined by subject self-assessment.
2. Number of Subjects Receiving Rescue Study Medication [ Time Frame: Within 4 h after start of study treatment ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Documented congenital C1-INH deficiency
• Acute facial or abdominal HAE attack

Key Exclusion Criteria:

• Acquired angioedema
• Treatment with any other investigational drug within the last 30 days before study entry
• Treatment with any C1-INH concentrate within the previous 7 days

Contacts and Locations

Locations

United States, California

Study Site

Granada Hills, California, United States, 91344

United States, Florida

Study Site

Weston, Florida, United States, 33331

United States, Georgia

Study Site

Atlanta, Georgia, United States, 30342

United States, Idaho

Study Site

Idaho Falls, Idaho, United States, 83404

United States, Illinois

Study Site

Chicago, Illinois, United States, 60612

United States, Louisiana

Study Site

Shreveport, Louisiana, United States, 71130

United States, Massachusetts

Study Site

Boston, Massachusetts, United States, 02115

United States, Minnesota

Study Site

Plymouth, Minnesota, United States, 55411

United States, Nebraska

Study Site

Omaha, Nebraska, United States, 68131

United States, New York

Study Site

Bronx, New York, United States, 10461

United States, Ohio

Study Site

Cincinnati, Ohio, United States, 45231

United States, Oklahoma

Study Site

Tulsa, Oklahoma, United States, 74133

United States, Oregon

Study Site

Eugene, Oregon, United States, 97401

United States, Pennsylvania

Study Site

Hershey, Pennsylvania, United States, 17033

United States, South Dakota

Study Site

Rapid City, South Dakota, United States, 57702

United States, Texas

Study Site

Dallas, Texas, United States, 75230

United States, Washington

Study Site

Bellingham, Washington, United States, 98225

Argentina

Study Site

Buenos Aires, Argentina

Australia

Study Site

Westmead, Australia

Bulgaria

Study Site

Plovdiv, Bulgaria

Study Site

Sofia, Bulgaria

Canada

Study Site

Edmonton, Canada

Study Site

Ottawa, Canada

Czech Republic

Study Site

Brno, Czech Republic

Hungary

Study Site

Budapest, Hungary

Israel

Study Site

Tel Hashomer, Israel

Macedonia, The Former Yugoslav Republic of

Study Site

Skopje, Macedonia, The Former Yugoslav Republic of

Poland

Study Site

Grodzisk Mazowiecki, Poland

Study Site

Krakow, Poland

Romania

Study Site

Tirgu-Mures, Romania

Russian Federation

Study Site 1

Moscow, Russian Federation

Study Site 2

Moscow, Russian Federation

Study Site 3

Moscow, Russian Federation

Spain

Study Site

Madrid, Spain

Sweden

Study Site

Goeteborg, Sweden

United Kingdom

Study Site

London, United Kingdom

Sponsors and Collaborators

CSL Behring

Investigators

• Study Director: Program Director, Clinical R&D; CSL Behring

More Information

Publications of Results:

Craig TJ, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz D, Obtułowicz K, Reshef A, Ritchie B, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Bernstein JA. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009 Oct;124(4):801-8. doi: 10.1016/j.jaci.2009.07.017. Epub 2009 Sep 19.

Other Publications:

Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtułowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Keinecke HO, Craig TJ. Hereditary angioedema: Validation of the end point time to onset of relief by correlation with symptom intensity. Allergy Asthma Proc. 2011 Jan-Feb;32(1):36-42. doi: 10.2500/aap.2011.32.3404.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Craig TJ, Rojavin MA, Machnig T, Keinecke HO, Bernstein JA. Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Sep;111(3):211-5. doi: 10.1016/j.anai.2013.06.021. Epub 2013 Jul 16.

Bernstein JA, Ritchie B, Levy RJ, Wasserman RL, Bewtra AK, Hurewitz DS, Obtulowicz K, Reshef A, Moldovan D, Shirov T, Grivcheva-Panovska V, Kiessling PC, Schindel F, Craig TJ. Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Aug;105(2):149-54. doi: 10.1016/j.anai.2010.06.005. Erratum in: Ann Allergy Asthma Immunol. 2011 Jan;106(1):78.

• Responsible Party: Global Head Clinical Research & Development, CSL Behring
• ClinicalTrials.gov Identifier: NCT00168103
• Other Study ID Numbers: CE1145_3001; 2004-001186-17 ( EudraCT Number )
• First Posted: September 14, 2005
• Results First Posted: August 24, 2010
• Last Update Posted: March 31, 2015
• Last Verified: February 2011

Keywords provided by CSL Behring:

C1 Inhibitor; Hereditary angioedema; Acute HAE attack

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Complement C1s; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; Immunosuppressive Agents